CXADR: From an Essential Structural Component to a Vital Signaling Mediator in Spermatogenesis
Abstract
:1. Introduction
2. Structure of the CXADR Protein and Gene
2.1. Structure of the CXADR Gene
2.2. Structure of the CXADR Protein
3. CXADR Knockout and Overexpression Mouse Models
4. Pathogeneses Associated with CXADR Dysregulation
5. Functions of CXADR
5.1. CXADR Functions as Structural Component of Tight and Adherens Junctions
5.2. CXADR Participates in and Regulates the Formation of Other Cell Junctions
5.3. An Emerging Role of CXADR as a Signaling Mediator
6. Regulation of CXADR
6.1. Ectodomain Shedding and Intramembrane Proteolysis
6.2. Cytokines
6.3. Components of Cell Junctions
6.4. MicroRNAs and E3 Ligase
7. Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Model | Exon | Time | Phenotypes | Reference |
---|---|---|---|---|
Cxadr−/− | 2 | E0 * | Embryonal lethal between E11.5 and E13.5 Thinner myocardial wall Cardiomyocytes degenerating Cardiomyocytes death | [26] |
Cxadr+/− | 2 | E0 | Normal | [26] |
Cxadr+/− | 1 | E0 | Normal | [27] |
Cxadr−/− | 1 | E0 | Embryonal lethal between E11.5 and E13.5 Reduced density of myofibrils Disorganized orientation and bundling of myofibrils Formation of pericardial edema | [27] |
Cxadr−/− | 2 | E0 | Embryonal lethal between E11.5 and E12.5, or die shortly after birth Regional over-proliferation of cardiomyocytes Hyperplasia of the left ventricle Abnormal junction between sinus venosus | [31] |
Cxadrflox/flox; Protamine-Cre | 2 | Cxadr-null sperm is still fertile | [31,32] | |
Cxadrflox/flox; TNT-Cre | 2 | E9.5 | Embryonal lethality | [31,33] |
Cxadrflox/flox; α-MHC-Cre | 2 | E11.5 | Viable | [31,34] |
Cxadrflox/flox; α-MHC-cre | 1 | Blockage of atrioventricular conduction in the adult heart Prolonged atrioventricular conduction in the embryonic heart Loss of connexin 45 Decreased β-catenin and ZO-1 amount and localization Cardiomyopathy | [34,35] | |
Cxadr−/− | 2 | Embryonal lethal between E11.5 and E12.5 Hemorrhage Pericardial effusion | [35] | |
Cxadrflox/flox; α-MHC-cre, Tamoxifen-Inducible | 1 | P2 months | Impaired electrical conductance from the atrium to ventricle Reduced expression of ZO-1 Reduced expression of connexin 45 Altered localization of connexin 43 | [36,37] |
Cxadrflox/flox; α-MHC-cre, Tamoxifen-Inducible | 1 | P2 months | Prevent signs of inflammatory cardiomyopathy after CVB3 | [37,38] |
Cxadrflox/flox; Cre-ERTM | 2 | P3 weeks | Dilated intestinal tract Atrophy of the exocrine pancreas Abnormal thymopoiesis | [39,40] |
Cxadrflox/flox; Cre-ERTM | 2 | E12.5 | Lethal Subcutaneous edema Hemorrhage Embryonic lethality Dilated subcutaneous lymphatic vessels Abnormal structure with gaps and holes presents at lymphatic endothelial cell-cell junctions Erythrocyte leakage | [39,41] |
Cxadrflox/flox; Cre-ERTM | 2 | E13.5 | Viable | [39,41] |
Cxadr+/− | 1 | Slower ventricular conduction Increased arrhythmia susceptibility Reduced sodium current magnitude | [29] | |
Cxadrflox/flox; Cre-ERTM | 2 | P4–6 weeks | Intact blood-testis barrier Uncompromised fertility No detectable phenotype up to the age of 8 months | [28,39] |
Cxadrflox/flox; Cre-ERTM | 2 | P8 | Intact blood-testis barrier uncompromised fertility | [28,39] |
Cxadrflox/flox; hNphs2-Cre | 1 | E14.0 | Normal podocyte development Normal stress response | [42,43] |
Cxadrflox/flox; Tnnt2-Cre | 1 | E7.5 | Embryonic lethality by E12.5 Thinner placentas Decreased labyrinth depth | [44,45] |
CxadrC210A/C210A-ENU | N.A. | Thinness of the labyrinth | [44] | |
Cxadrflox/flox; Myh-6-Cre | 1 | Viable No obvious labyrinth defects | [34,44] | |
Cxadrflox/flox; Sox2-Cre | 1 | E14.5 | Lethal between E11.5 and E12.5 Altered interheamal membrane architecture Reduced IHM branching Flatter placentas | [44,46] |
Cxadrflox/flox; Stra8-iCre | 3 | P8 | No observable changes in reproductive functions; | [47,48] |
Cxadrflox/flox; Amh-Cre | 3 | E14.5 | Reduced fertility with age Increased germ cell apoptosis Premature loss of elongated spermatids Compromised BTB function and apical ES structure Dysregulation of occludin and ZO-1 Altered β-catenin/Cdc42 signaling | [47,49] |
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Share and Cite
Zhang, Y.; Lui, W.-Y. CXADR: From an Essential Structural Component to a Vital Signaling Mediator in Spermatogenesis. Int. J. Mol. Sci. 2023, 24, 1288. https://doi.org/10.3390/ijms24021288
Zhang Y, Lui W-Y. CXADR: From an Essential Structural Component to a Vital Signaling Mediator in Spermatogenesis. International Journal of Molecular Sciences. 2023; 24(2):1288. https://doi.org/10.3390/ijms24021288
Chicago/Turabian StyleZhang, Yang, and Wing-Yee Lui. 2023. "CXADR: From an Essential Structural Component to a Vital Signaling Mediator in Spermatogenesis" International Journal of Molecular Sciences 24, no. 2: 1288. https://doi.org/10.3390/ijms24021288